tbuckley/cabot-search huggingface dataset:
Delivery of therapeutic carbon monoxide by gas-entrapping materials
Authors: James D. Byrne, David Gallo, Hannah Boyce, Sarah L. Becker, Kristi M. Kezar, Alicia T. Cotoia, Vivian R. Feig, Aaron Lopes, Eva Csizmadia, Maria Serena Longhi, Jung Seung Lee, Hyunjoon Kim, Adam J. Wentworth, Sidharth Shankar, Ghee Rye Lee, Jianling Bi, Emily Witt, Keiko Ishida, Alison Hayward, Johannes L. P. Kuosmanen, Josh Jenkins, Jacob Wainer, Aya Aragon, Kaitlyn Wong, Christoph Steiger, William R. Jeck, Dustin E. Bosch, Mitchell C. Coleman, Douglas R. Spitz, Michael Tift, Robert Langer, Leo E. Otterbein, Giovanni Traverso
Journal: Science Translational Medicine (2022)

Carbon monoxide (CO) has long been considered a toxic gas but is now a recognized bioactive gasotransmitter with potent immunomodulatory effects. Although inhaled CO is currently under investigation for use in patients with lung disease, this mode of administration can present clinical challenges. The capacity to deliver CO directly and safely to the gastrointestinal (GI) tract could transform the management of diseases affecting the GI mucosa such as inflammatory bowel disease or radiation injury. To address this unmet need, inspired by molecular gastronomy techniques, we have developed a family of gas-entrapping materials (GEMs) for delivery of CO to the GI tract. We show highly tunable and potent delivery of CO, achieving clinically relevant CO concentrations in vivo in rodent and swine models. To support the potential range of applications of foam GEMs, we evaluated the system in three distinct disease models. We show that a GEM containing CO dose-dependently reduced acetaminophen-induced hepatocellular injury, dampened colitis-associated inflammation and oxidative tissue injury, and mitigated radiation-induced gut epithelial damage in rodents. Collectively, foam GEMs have potential paradigm-shifting implications for the safe therapeutic use of CO across a range of indications.
POS1246 COVID-19 IN RITUXIMAB TREATED PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES
Authors: R. Hasseli, B. F. Hoyer, H. M. Lorenz, A. Pfeil, A. Regierer, J. Richter, T. Schmeiser, A. Strangfeld, R. Voll, H. Schulze-Koops, A. Krause, C. Specker, U. Müller-Ladner
Journal: Annals of the Rheumatic Diseases (2022)

Background At the beginning of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease 2019 (COVID-19) pandemic, the influence of anti-inflammatory therapy on the course of SARS-CoV-2 infection in patients with inflammatory rheumatic diseases (IRD) was unknown. In the meantime, several data indicate an association of severe courses of COVID-19 with the use of rituximab (RTX). Objectives To gather further knowledge about SARS-CoV-2 infections in RTX-treated IRD patients, data from the German COVID-19-IRD-registry were analysed. Methods Hospitalisation was used as a surrogate of COVID-19 severity. Baseline characteristics, disease features, medication and outcome of COVID-19 were compared in RTX-treated inpatients and outpatients. Results In total, 3592 cases were reported in the registry, which included 130 RTX patients (3.6%) for our analysis. RTX-treated inpatients were older than RTX-treated outpatients (median age 63 y vs 56 y, p=0.007). Patients with granulomatosis with polyangiitis treated with RTX (n=32) showed a significant higher COVID-19 related hospitalisation rate (33% vs 11%, p=0.005), which was not the case for patients with rheumatoid arthritis (49% vs 50%). Cardiovascular comorbidities were reported more frequently in hospitalised RTX-treated patients (20% vs. 6%, p=0.032). More than 50% of the RTX-treated inpatients developed COVID-19 related complications, e.g. acute respiratory distress syndrome. The median time period between the last RTX treatment and SARS-CoV-2 infection was shorter in inpatients than in non-hospitalised patients (3 (range 0-17) vs. 4 months (range -29), p=0.039). The COVID-19 related mortality rate was 14% (n=19) in RTX-treated IRD patients. In RTX-treated inpatients and outpatients, there were no relevant differences with respect to the use of concomitant glucocorticoids or other disease modifying anti-rheumatic drugs, disease activity, median last RTX dose or median number of immunomodulatory drugs prior to RTX treatment. Conclusion In addition to general risk factors, such as age and comorbidities, it is already known that IRD patients treated with RTX show a higher rate of severe COVID-19. In our registry, RTX-treated patients with granulomatosis with polyangiitis appear to be at even higher risk to develop severe COVID-19 compared to other IRD. Moreover, the shorter the time since the last RTX treatment, the higher seems to be the risk of developing severe COVID-19. This might be explained by a more profound B-cell depletion in the first weeks after RTX treatment warranting further studies. Disclosure of Interests None declared
AB1316 PREVALENCE, DIAGNOSTIC DELAY AND TREATMENT PROFILE OF PATIENTS WITH MONOGENIC AUTOINFLAMMATORY DISEASES IN AN ADULT RHEUMATOLOGY SERVICE OF A TERTIARY HOSPITAL.
Authors: C. Pávez Perales, E. Molina Rus, E. Grau García, M. De la Rubia Navarro, S. Leal Rodriguez, C. Riesco Barcena, A. V. Huaylla Quispe, P. Muñoz Martinez, L. Mas Sanchez, J. Ivorra Cortés, J. E. Oller Rodríguez, J. J. Fragío Gil, R. González Mazarío, I. Cánovas Olmos, I. Martínez Cordellat, E. Vicens Bernabeu, F. Ortiz-Sanjuán, R. Negueroles Albuixech, L. Gonzalez Puig, C. Nájera Herranz, J. A. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2022)

Background Monogenic autoinflammatory diseases (MAISs) have a low prevalence and a delay in their diagnosis, with the risk of complications being AA amyloidosis the most serious. Biological therapy has been a fundamental pillar in improving the prognosis of these diseases, reducing said risk. Objectives We aim to study the prevalence, diagnostic delay and treatment profile of MAISs patients in an adult rheumatology service of a tertiary hospital. Methods Observational and retrospective study of patients with MAISs, excluding those without genetic test or negative genetic test, with a follow-up period of 17 years (2005-2021). Demographic, clinical and therapeutic variables were collected. Results 24 patients (50% men) were included with a mean age of 27,88 ± 11.57y. The prevalence of MAISs was 0.34%, from a total of 7,032 patients followed up in the Rheumatology service during 2020. Familial Mediterranean Fever (FMF) was the most frequent (70.83%). FMF, Tumor Necrosis Factor Receptor Associated Periodic Syndrome (TRAPS), and Hyperimmunoglobulin D Syndrome (HIDS) had a median age at symptom onset of 6, 8.5 and 2 years, a median diagnostic delay of 6, 8.75 and 11 years and a mean duration of the bouts of 4.47 (2.87), 12.25 (7.59) and 6 (2.65) days, respectively. The most frequent symptoms were: fever (79.17%), arthralgia/arthritis (79.17%) and abdominal pain (75%). During follow up 20.83% received glucocorticoids (GC) chronically (more than 3 months), 79.16% colchicine, 16.66% methotrexate and 41.66% biological therapies (Table 1). At the end of follow up 4.17% were receiving GC, 79.16% colchicine, 4.16% methotrexate and 33.33% biological therapies (Table 1). No AA amyloidosis or deaths were reported. Table 1. MAISs Gender (men % ) Biological therapies prescribed during follow up (n ) Patients under biological therapies at the end of follow up (n ) FMF (n=17 ) 41.17% Anakinra: 2 Anakinra: 3 Canakinumab: 2 Canakinumab: 2 Etanercept: 1 Tocilizumab: 1 TRAPS (n=4 ) 100% Anakinra: 1 Canakinumab: 1 Canakinumab: 1 Etanercept: Tocilizumab: HIDS (=3 ) 66.66% Anakinra: 3 Canakinumab: 2 Canakinumab: 3 Etanercept. 1 Conclusion MAISs prevalence was 0.34%. The diagnostic delay was of years, more than a decade for HIDS. Colchicine was widely used and well tolerated. Synthetic DMARDs had little role in treatment. Biological therapies were prescribed in a third of patients, anti IL-1 being the most used. Disclosure of Interests None declared
AB1505 MOROCCAN MEDICAL STUDENTS SURVEY: WHAT ARE THE MOTIVATIONS AND BARRIERS TO CHOOSE RHEUMATOLOGY AS A CAREER?
Authors: A. Anass, T. Fatima Zahrae, N. Takhrifa, B. Khadija, F. Abourazzak
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatology has experienced a genuine progress in recent decades, especially with the development of new treatments and the use of ultrasound as a mean of exploring the musculoskeletal system, which has contributed to its attractiveness for medical students. Objectives The objective of this survey is to study the factors that motivate or discourage medical students to choose rheumatology as a career. Methods Web-based questionnaire was sent to 297 medical students who had begun their Hospital training, 100 medical interns, and 280 general practice graduates after passing the residency program’s examinations and before choosing their specialty. This questionnaire covered three areas: anonymous demographic information, attitudes toward rheumatology as a specialty, and reasons behind choosing or not choosing rheumatology (multiple choice and open-ended questions). Results We collected responses from 161 students (answer rate: 54%), 68 interns (68%), and 89 (32%) medical school graduates. 41.6% of students and 43.8% of graduates consider that they can choose rheumatology as a specialty, whereas 11.2% of students, 5.9% of interns and 7.9% of graduates considered rheumatology as their dream career. The main motivation for students to choose rheumatology is “the diversity of the musculoskeletal pathology”. According to interns and graduates, the benefit of choosing rheumatology is the quality of life it can offer, given that it is a “relatively less time consuming specialty». The main barrier to choose rheumatology is “the interest in surgical specialties” for students and interns and ‘‘the limited therapeutic aspects’’ for graduates. Other commonly reported reasons are shown in Table 1. Table 1. Main motivations and barriers to choose rheumatology according to Moroccan medical students, interns and medical graduates. Motivations Students Interns Graduates N=67 N=4 N=39 -Wide-ranging specialty with diversity of musculoskeletal pathologies 48 (71,6 %) 2 (50 %) 11 (28,2 %) 24 (35,8 %) 2 (50 %) 10 (25,6 %) 19 (28,4 %) 3 (75 %) 28 (71,8 %)2 - - -Interventional aspect of rheumatology: ultrasound guided injections, biopsy, Hydrodilatation. - - -Relatively less time-consuming specialty Barriers N=88 N=62 N=50 -I am interested in surgical specialties 44 (50 %) 32 (49,2 %) 23 (46 %) 21 (23,9 %) 12 (18,5 %) 21 (42 %) 22 (25 %) 18 (27,7 %) 26 (52 %) - -Monotonous specialty - -Limited therapeutic aspects Conclusion Our study has shown that rheumatology fascinates Moroccan medical students by its clinical abundance and the diversity of musculoskeletal pathology and also by the quality of life it can offer. According to the students, the main barriers to choose rheumatology are the interest in a surgical specialty, and the limited therapeutic aspects of the specialty. Disclosure of Interests None declared
AB0054 NEW THERAPEUTICAL TOOLS FOR HETEROTOPIC OSSIFICATION TREATMENT AND PREVENTION
Authors: A. Alonso-Pérez, M. Guillán-Fresco, E. Franco-Trepat, A. Lois-Iglesias, A. Jorge-Mora, R. Gómez
Journal: Annals of the Rheumatic Diseases (2022)

Background Heterotopic ossification (HO) consists in abnormal bone growth in soft tissues, in a non-porrostoeblastogenic environment. This pathology origin can be congenital (progressive osseus heteroplasia, progressive osseous fibrodysplasia, …) or acquired (burnt, big traumas, electrocutions, articular replacement surgeries, …). Currently, the available therapies (radiotherapy and removal surgery) are aggressive, associated to multiple adverse effects, and not suitable for every populations. Therefore, new therapeutic tools are needed to HO. Osteoblast is the cell type in charge of bone growth. These cells share a mesenchymal origin with adipocytes. Interestingly, osteoblastogenesis and adipogenesis are opposed and mutually controlled processes. Objectives The aim of this work is to study osteoblastogenesis inhibition through adipogenesis promotion using a new therapy (Tri-therapy) composed by a PPARG agonist, a NSAID, and a corticoid. Methods Mice mesenchymal stem cells (C3H10T1/2) were differentiated towards adipogenesis and osteoblastogenesis for 7 days, in the presence of the Tri-therapy compounds alone and combined. Simultaneously, human preosteoblast cells (SaOS2) were differentiated to osteoblast for 14 days, being treated with the Tri-therapy. Human HO cells (acquired HO and congenital HO independently), obtained from HO explants, were exposed to an adipogenic environment in the presence of the Tri-therapy for 7 days. Osteoblastogenic (ALPL, SPP1, GPNMB, RUNX2) and adipogenic (FABP4, PLIN2, ADIPOQ, PPARG) marker genes mRNA expression measured by RT-PCR was used to evaluate differentiation processes. All the results were expressed as the media± SEM of, at least, 3 independent replicates. Results In C3H10T1/2 differentiations Tri-therapy synergically induced FABP4, PLIN2, ADIPOQ expression in both cell fates, demonstrating therefore its ability to promote adipogenesis. In SaOS2, the proposed therapy diminished osteoblastogenic marker genes expression (SPP1, GPNMB, RUNX2), being this effect greater than PPARG agonists’ themselves. In HO cells, Tri-therapy augmented adipogenesis markers expression, showing a partial effect in osteoblastogenic marker genes expression. Conclusion Pro-adipogenic switch in differentiation marker genes expression induced by the Tri-therapy suggested the clinical use of this drugs combination to treat and prevent HO and abnormal bone growth. Disclosure of Interests None declared
Core transcription programs controlling injury-induced neurodegeneration of retinal ganglion cells
Authors: Feng Tian, Yuyan Cheng, Songlin Zhou, Qianbin Wang, Aboozar Monavarfeshani, Kun Gao, Weiqian Jiang, Riki Kawaguchi, Qing Wang, Mingjun Tang, Ryan Donahue, Huyan Meng, Yu Zhang, Anne Jacobi, Wenjun Yan, Jiani Yin, Xinyi Cai, Zhiyun Yang, Shane Hegarty, Joanna Stanicka, Phillip Dmitriev, Daniel Taub, Junjie Zhu, Clifford J. Woolf, Joshua R. Sanes, Daniel H. Geschwind, Zhigang He
Journal: Neuron (2022)
AB1290 SOMETIMES IT IS ALL IN THE HEART; CARDIAC INVOLVEMENT IN BEHCET’S SYNDROME
Authors: R. Yildirim, M. Dinler, N. S. Yasar Bilge, T. Kaşifoğlu
Journal: Annals of the Rheumatic Diseases (2022)

Background Cardiac involvement is an uncommonly seen but might be a fatal clinical manifestation of Behcet’s syndrome (BS), if not recognized early and treated aggressively. Objectives Our aim was to retrospectively evaluate the characteristics of cardiac involvement in Behcet’s syndrome and investigate possible risk factors. Methods 800 patients with BS diagnosis according to International Study Group for Behcet’s Disease (ISG) criterias in our center were screened. 14 patients with cardiac involvement were included in this study. Results All the patients were male with positive smoking history. The age at the onset cardiac involvement was 32.5 ± 7.8 years. In 3 patients, diagnosis of BS was made simultaneously with cardiac involvement. Types of cardiac involvement were as following; intracardiac thrombosis (ICT) in 8, right coronary artery aneurysm in 2, and myocardial infarction in 4 patients. The majority of ICT was seen in right ventricle followed by right atrium (75% vs 25%). Deep vein thrombosis (DVT) was the most common accompanying other vascular involvement (57%).Thrombophilic factors were studied in 8 patients, whom only 2 cases were found positive for heterozygous factor V Leiden mutation. Cyclophosphamide was the most common used immunosuppressive agent and anticoagulation was used in 9 patients (Table 1). Table 1. Characteristics of cardiac involvement in BS patients Male/female, (n), (%) 14 (100%) Diagnosis age, years (Mean ± SD) 30 ± 7 Age of cardiac involvement, years, (Mean ± SD) 32.5 ±7.8 Smoking history, (n), (%) 14 (100%) Other vascular involvement, (n), (%) 12 (85%) -Deep vein thrombosis, (n) 8 -Pulmonary involvement, (n) 4 -Peripheral artery aneurysm, (n) 1 Cardiac involvement patterns -ICT, (n), (%) •RV 6 •RA 2 -CAA, (n), (%) 2(14.3%) -AMI, (n), (%) 4(28.6%) Immunosuppression, (n) -Steroid 14 -CYC 9 -AZA 3 -IFN 1 Anticoagulation, (n) 9 ICT; intracardiac thrombosis, RV; right ventricle, RA; right atrium, CAA; coronary artery aneurysm, AMI; acute myocardial infarction, CYC; cyclophopshamide, AZA; azathioprine, IFN; interferon Conclusion Most common type of cardiac involvement is pericarditis, whereas intracardiac thrombosis has its unique characteristics (1). Male gender and smoking seems to be major significant risk factors. References [1]Wang H, Guo X, Tian Z, Liu Y, Wang Q, Li M, Zeng X, Fang Q (2016) Intracardiac thrombus in patients with Behcet’s disease: clinical correlates, imaging features, and outcome: a retrospective, single-center experience. Clinical Rheumatology 35(10):2501–2507 Disclosure of Interests None declared
AB1161 COVID-19 IN MY RA CLINIC: DATA FROM QUESTIONNAIRE, VACCINATION, INFECTION AND FLARES FROM THE RA LOUVAIN BRUSSELS COHORT
Authors: V. Pirson, T. Sokolova, X. Theunssens, L. Bricman, E. Sapart, S. DE Montjoye, S. Dierckx, A. Avramovska, P. Durez
Journal: Annals of the Rheumatic Diseases (2022)

Background Over 5 million deaths from the COVID-19 disease have been reported in the world. Patients (pts) living with rheumatoid arthritis (RA) affecting the immune system or under immunosuppressive agent are considered as a high risk population for a SARS-CoV-2 infection. Since no antiviral treatment is available, the vaccination is a major option. Objectives The aim of this study is to evaluate in our RA cohort a questionnaire about the COVID-19 vaccination willingness, to analyse the vaccination rate, the number of COVID infection, the RA flares and the side effects. Methods We included pts with RA from the UCLouvain Brussels cohort who met the ACR/EULAR 2010 classification criteria. A simple and standard questionnaire about the vaccine willingness was distributed in 2020 before the vaccination. From January to December 21, the rate of vaccination was calculated. The number of Covid infections, RA flares, therapy switches and side effects were also collected. All patient and RA characteristics were analyzed. Results 605 eligible RA pts were included. The average age of the population is 58.21 years. 72% of the patients are women. 21% are smokers and 65% are positive for anti-citrullinated protein antibody (ACPA) with a mean DAS28-CRP of 2.39 and a mean HAQ of 0.821. In 2020, 460 pts filled the questionnaire and 61% indicated they would receive the vaccine as soon as it is available. For the 179 pts (39%) who decline, the reasons for not having vaccine were no trust in the vaccine at this time (53%), fear of side effects (28%), opposition to vaccine (4%), previous SARS-CoV-2 infection (2%) and unknown (5%). Pts under the age of 50, women, low education grade, smokers, presence of RF/ACPA and treatment with a bioDMARD were less willing to receive the vaccine. In 2021, 538 pts were vaccinated and only 67 pts (11.1%) not. The majority received a mRNA vaccine (81.8%). 72 and 21 pts developed a SARS-CoV-2 infection before and after the vaccination, respectively. Among them, 5 were admitted to intensive care unit leading to 4 deaths. Only, 7 RA flares were observed and 17 pts switched the therapy. 101 adverse events were reported. All of them were mild and transient except 2 cases with pulmonary embolism and one case with Herpes Zooster infection. Conclusion The SARS-COV-2 global pandemic is responsible of many medical dramas. In our RA cohort, we observed first hesitation followed by a high rate of vaccination. The safety was reassuring with a minimal number of RA flares and serious adverse events including only 4 deaths. Acknowledgements This work was supported by CAP48/RTBF. Disclosure of Interests None declared
Widespread redundancy in -omics profiles of cancer mutation states
Authors: Jake Crawford, Brock C. Christensen, Maria Chikina, Casey S. Greene
Journal: Genome biology (2022)

Abstract Background In studies of cellular function in cancer, researchers are increasingly able to choose from many -omics assays as functional readouts. Choosing the correct readout for a given study can be difficult, and which layer of cellular function is most suitable to capture the relevant signal remains unclear. Results We consider prediction of cancer mutation status (presence or absence) from functional -omics data as a representative problem that presents an opportunity to quantify and compare the ability of different -omics readouts to capture signals of dysregulation in cancer. From the TCGA Pan-Cancer Atlas that contains genetic alteration data, we focus on RNA sequencing, DNA methylation arrays, reverse phase protein arrays (RPPA), microRNA, and somatic mutational signatures as -omics readouts. Across a collection of genes recurrently mutated in cancer, RNA sequencing tends to be the most effective predictor of mutation state. We find that one or more other data types for many of the genes are approximately equally effective predictors. Performance is more variable between mutations than that between data types for the same mutation, and there is little difference between the top data types. We also find that combining data types into a single multi-omics model provides little or no improvement in predictive ability over the best individual data type. Conclusions Based on our results, for the design of studies focused on the functional outcomes of cancer mutations, there are often multiple -omics types that can serve as effective readouts, although gene expression seems to be a reasonable default option.